ribA2 Resolved · high auto-curated
H37Rv Rv1415 · MTBC0 mtbc0_001515 ·
425 aa · 1599741–1601018 (+) ·
RefSeq NP_215931.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional 3%2C4-dihydroxy-2-butanone-4-phosphate synthase/GTP cyclohydrolase II |
| Revised (this work) | Bifunctional 3%2C4-dihydroxy-2-butanone-4-phosphate synthase/GTP cyclohydrolase II. Pfam: DHBP_synthase (PF00926.25), GTP_cyclohydro2 (PF00925.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHF1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Riboflavin biosynthesis protein RibBA [Includes: 3,4-dihydroxy-2-butanone 4-phosphate synthase |
| EC (curated) |
EC 3.5.4.25, EC 4.1.99.12
|
| Curated function | Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate..; FUNCTION: Catalyzes the conversion of GTP to 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (DARP), formate and pyrophosphate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | ribBA |
| eggNOG description | Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate |
| Orthologous group | COG0108 |
| EC number |
EC 3.5.4.25, EC 4.1.99.12
|
| KEGG orthology |
K14652
|
| KEGG pathways |
map00740, map00790, map01100, map01110
|
| KEGG modules |
M00125, M00840
|
| Gene Ontology (4) |
GO:0005575, GO:0005576, GO:0008150, GO:0040007
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.507 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DHBP_synthase | PF00926.25 | 1.9e-84 | 8–201 | 3,4-dihydroxy-2-butanone 4-phosphate synthase |
GTP_cyclohydro2 | PF00925.26 | 1.3e-73 | 210–381 | GTP cyclohydrolase II |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ribH (6,7-dimethyl-8-ribityllumazine synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1416 ribH |
6,7-dimethyl-8-ribityllumazine synthase | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:986 database:900 textmining:885 |
Rv1412 ribC |
riboflavin synthase | 999 | 1000 ctx | neighborhood:505 fusion:896 cooccurence:774 coexpression:985 textmining:418 |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 999 | 1000 ctx | neighborhood:544 fusion:519 cooccurence:772 coexpression:980 experimental:759 database:900 textmining:812 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 943 | 921 | database:900 |
Rv3609c folE |
GTP cyclohydrolase I | 964 | 916 | database:900 textmining:593 |
Rv3109 moaA1 |
cyclic pyranopterin monophosphate synthase | 907 | 904 | database:900 |
Rv0869c moaA2 |
molybdenum cofactor biosynthesis protein MoaA | 907 | 904 | database:900 |
Rv1417 |
membrane protein | 902 | 902 ctx | neighborhood:881 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 904 | 899 | database:800 |
Rv2583c relA |
bifunctional (p)ppGpp synthase/hydrolase RelA | 841 | 835 | database:800 |
Rv1418 lprH |
lipoprotein LprH | 826 | 827 ctx | neighborhood:824 |
Rv3645 |
transmembrane protein | 814 | 814 | database:800 |
Rv1625c cya |
adenylate cyclase | 811 | 812 | database:800 |
Rv1320c |
adenylate cyclase | 810 | 811 | database:800 |
Rv1264 |
adenylyl cyclase | 810 | 811 | database:800 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase
- MTBC0 PGAP product: bifunctional 3%2C4-dihydroxy-2-butanone-4-phosphate synthase/GTP cyclohydrolase II
- Pfam (hmmscan --cut_ga): DHBP_synthase PF00926.25 (E=2e-84), GTP_cyclohydro2 PF00925.26 (E=1e-73)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215931.1)
- Domains: Pfam-A via hmmscan --cut_ga — DHBP_synthase (PF00926.25), GTP_cyclohydro2 (PF00925.26)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0108 - Curated reference: UniProt P9WHF1 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
130 functional partner(s); context anchor
ribH - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001515|Rv1415|ribA2 MTRLDSVERAVADIAAGKAVIVIDDEDRENEGDLIFAAEKATPEMVAFMVRYTSGYLCVPLDGAICDRLGLLPMYAVNQDKHGTAYTVTVDARNGIGTGISASDRATTMRLLADPTSVADDFTRPGHVVPLRAKDGGVLRRPGHTEAAVDLARMAGLQPAGAICEIVSQKDEGSMAHTDELRVFADEHGLALITIADLIEWRRKHEKHIERVAEARIPTRHGEFRAIGYTSIYEDVEHVALVRGEIAGPNADGDDVLVRVHSECLTGDVFGSRRCDCGPQLDAALAMVAREGRGVVLYMRGHEGRGIGLMHKLQAYQLQDAGADTVDANLKLGLPADARDYGIGAQILVDLGVRSMRLLTNNPAKRVGLDGYGLHIIERVPLPVRANAENIRYLMTKRDKLGHDLAGLDDFHESVHLPGEFGGAL